The proposed studies will examine an alternative model for regulation of the PRL gene. The specific aims include: 1) Determine the role that the mitogen activated protein kinase (MAPK) pathway plays in mediating the ability of cAMP and thyrotropin releasing hormone (TRH) to stimulate expression of the PRL gene. These studies will involve attempts to block activation of the MAPK pathways. The ability of cAMP and TRH to activate specific MAPK pathways will also be determined. This aim will test the possibility that a non-receptor tyrosine kinase plays an important role in linking the TRH receptor to the MAPK pathway. A possible role for the Ras superfamily member, Rap1b in mediating cAMP-induced activation of the PRL promoter will also be examined. 2) Explore the mechanisms which permit the LIM-homeodomain transcription factor, mLIM3, to enhance MAPK responsiveness of the PRL gene.